Differential Distribution of Major Brain Gangliosides in the Adult Mouse Central Nervous System

Katarina Vajn,Ronald L Schnaar,Barbara Viljetić,Ivan Večeslav Degmečić,Marija Heffer,David J Schulz

doi:10.1371/journal.pone.0075720

Katarina Vajn, Ronald L Schnaar + Show 4 more

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https://doi.org/10.1371/journal.pone.0075720

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Abstract

Gangliosides - sialic acid-bearing glycolipids - are major cell surface determinants on neurons and axons. The same four closely related structures, GM1, GD1a, GD1b and GT1b, comprise the majority of total brain gangliosides in mammals and birds. Gangliosides regulate the activities of proteins in the membranes in which they reside, and also act as cell-cell recognition receptors. Understanding the functions of major brain gangliosides requires knowledge of their tissue distribution, which has been accomplished in the past using biochemical and immunohistochemical methods. Armed with new knowledge about the stability and accessibility of gangliosides in tissues and new IgG-class specific monoclonal antibodies, we investigated the detailed tissue distribution of gangliosides in the adult mouse brain. Gangliosides GD1b and GT1b are widely expressed in gray and white matter. In contrast, GM1 is predominately found in white matter and GD1a is specifically expressed in certain brain nuclei/tracts. These findings are considered in relationship to the hypothesis that gangliosides GD1a and GT1b act as receptors for an important axon-myelin recognition protein, myelin-associated glycoprotein (MAG). Mediating axon-myelin interactions is but one potential function of the major brain gangliosides, and more detailed knowledge of their distribution may help direct future functional studies.

Highlights

Gangliosides, sialic acid-containing glycosphingolipids, are expressed widely in vertebrate tissues but at high abundance in the brain, where they are major cell surface determinants on nerve cells
General Expression Patterns of Major Brain Gangliosides The expression patterns of gangliosides GM1, GD1a, GD1b and GT1b were studied using immunohistochemistry on adult C57Bl/6 mouse brains and spinal cords cut in three planes
Expression patterns of the other three major brain gangliosides appear to be enhanced in certain brain regions

Summary

Introduction

Gangliosides, sialic acid-containing glycosphingolipids, are expressed widely in vertebrate tissues but at high abundance in the brain, where they are major cell surface determinants on nerve cells. Gangliosides are found primarily in the outer leaflet of plasma membranes where they are anchored via their ceramide lipid moiety, with their glycan structures extending into the extracellular space. They engage molecules laterally - in their own membranes - to regulate cell signaling, and they engage molecules on apposing cells to regulate cell-cell interactions. Mice genetically engineered to lack major brain gangliosides appear to develop normally, but demonstrate progressive nervous system deficits, especially in axon-myelin interactions [3]. A rare human genetic disorder resulting in congenital loss of complex gangliosides is more severe, resulting in neuromuscular and cognitive developmental stagnation, blindness, and seizures [4]

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